METHODS: In a pilot cross-sectional study of 37 incident breast cancer patients, fecal samples collected prior to chemotherapy were analyzed by 16S ribosomal RNA (rRNA) gene-based sequencing protocol. Alpha diversity and specific taxa by tumor characteristics and breast cancer risk factors were tested by Wilcoxon rank sum test, and by differential abundance analysis, using a zero-inflated negative binomial regression model with adjustment for total counts, age and race/ethnicity.
RESULTS: There were no significant alpha diversity or phyla differences by estrogen/progesterone receptor status, tumor grade, stage, parity and body mass index. However, women with human epidermal growth factor receptor 2 positive (HER2+) (n = 12) compared to HER2- (n = 25) breast cancer showed 12-23% lower alpha diversity [number of species (OTU) p = 0.033, Shannon index p = 0.034], lower abundance of Firmicutes (p = 0.005) and higher abundance of Bacteroidetes (p = 0.089). Early menarche (ages ≤ 11) (n = 11) compared with later menarche (ages ≥ 12) (n = 26) was associated with lower OTU (p = 0.036), Chao1 index (p = 0.020) and lower abundance of Firmicutes (p = 0.048). High total body fat (TBF) (> 46%) (n = 12) compared to lower (≤ 46%) TBF was also associated with lower Chao 1 index (p = 0.011). There were other significant taxa abundance differences by HER2 status, menarche age, as well as other tumor and breast cancer risk factors.
CONCLUSIONS: Further studies are needed to identify characteristics of the human microbiome and the interrelationships between breast cancer hormone receptor status and established breast cancer risk factors.
方法:在一项针对37例乳腺癌患者的试点横断面研究中,通过基于16S核糖体RNA(rRNA)基因的测序方案分析化疗前收集的粪便样品。通过Wilcoxon秩和检验检测了肿瘤特征和乳腺癌危险因素的α多样性和特定分类群,通过差异丰度分析,使用零膨胀负二项回归模型,对总计数进行调整,年龄和种族/民族。
结果:雌激素/孕激素受体状态没有明显的α多样性或门系差异,肿瘤分级,舞台,奇偶校验和体重指数。然而,与人表皮生长因子受体2阳性(HER2+)(n=12)相比,HER2-(n=25)乳腺癌的女性显示α多样性降低12-23%[物种数(OTU)p=0.033,Shannon指数p=0.034],厚壁菌丰度较低(p=0.005),拟杆菌丰度较高(p=0.089)。初潮早期(≤11岁)(n=11)与初潮晚期(≥12岁)(n=26)相比,OTU较低(p=0.036)。Chao1指数(p=0.020)和较低的Firmicutes丰度(p=0.048)。较高的总脂肪(TBF)(>46%)(n=12)与较低(≤46%)的TBF也与较低的Chao1指数有关(p=0.011)。HER2状态存在其他显着的分类群丰度差异,初潮年龄,以及其他肿瘤和乳腺癌危险因素。
结论:需要进一步的研究来确定人类微生物组的特征以及乳腺癌激素受体状态与已确定的乳腺癌危险因素之间的相互关系。